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O Lund

Publications and source records attributed to O Lund.

At least 37 records · Page 2Linked to original sources
PubMed1998

NetOglyc: prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility.

The specificities of the UDP-GalNAc:polypeptide Nacetylgalactosaminyltransferases which link the carbohydrate GalNAc to the side-chain of certain serine and threonine residues in mucin type glycoproteins, are presently unknown. The specificity seems to be modulated by sequence context, secondary structure and surface accessibility. The sequence context of glycosylated threonines was found to differ from that of serine, and the sites were found to cluster. Non-clustered sites had a sequence context different from that of clustered sites. Charged residues were disfavoured at position -1 and +3. A jury of artificial neural networks was trained to recognize the sequence context and surface accessibility of 299 known and verified mucin type O-glycosylation sites extracted from O-GLYCBASE. The cross-validated NetOglyc network system correctly found 83% of the glycosylated and 90% of the non-glycosylated serine and threonine residues in independent test sets, thus proving more accurate than matrix statistics and vector projection methods. Predictions of O-glycosylation sites in the envelope glycoprotein gp120 from the primate lentiviruses HIV-1, HIV-2 and SIV are presented. The most conserved O-glycosylation signals in these evolutionary-related glycoproteins were found in their first hypervariable loop, V1. However, the strain variation for HIV-1 gp120 was significant. A computer server, available through WWW or E-mail, has been developed for prediction of mucin type O-glycosylation sites in proteins based on the amino acid sequence. The server addresses are http://www.cbs.dtu.dk/services/NetOGlyc/ and netOglyc@cbs.dtu.dk.

Algorithms↗
PubMed1998

Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis.

BACKGROUND: Long-term results after aortic value replacement for aortic stenosis can be correlated to a cardiac-related pre-operative risk profile. This predictability indicates that there is a common basis in subtle or overt structural abnormalities of left ventricular myocardium. METHODS AND RESULTS: Forty-nine patients aged 24-82 (mean 61) years, with aortic stenosis had a full wall thickness transmural biopsy of the left ventricular antero-lateral free wall during aortic valve replacement. Echocardiography and radionuclide ventriculography were performed prior to, and 18 months (n = 41) after, the operation. Postoperative follow-up to a maximum of 7.7 years was 100% complete. Pre-operatively, all patients had an increase in both the left ventricular mass index (202 +/- 67 g.m-2) and the muscle cell diameter (41 +/- 8 microns); other morphological data included a muscle cell nucleus volume of 752 +/- 192 microns3, a muscle cell mass index of 163 +/- 54.m-2, and a fibrous tissue mass index of 39 +/- 16 g.m-2. Patients with a pre-operative episode of clinical left ventricular failure (n = 19) had significantly greater morphological variables than those without. Pre-operative ejection fraction and other measures of systolic function correlated inversely with the morphological data, except for the fibrous tissue mass index; diastolic function indices correlated inversely with all the morphological variables. At the 18-month re-study, the same general picture was noted, but with an underlying strengthening, especially of the muscle cell mass index. Overall, the mass index dropped to 152 +/- 51 g.m-2 (P < 0.0001), but in 17% of the patients it became normal; the mass index at 18 months was directly correlated to morphological variables. A high muscle cell nucleus volume was identified as an independent predictor of early and late mortality. CONCLUSIONS: Abnormalities of the hypertrophied left ventricular muscle cell and the degree of muscle hypertrophy are, to some degree, underlying determinants of pre-operative symptomatology, pre- and postoperative ventricular function, and early and late mortality after valve replacement for aortic stenosis. Incomplete hypertrophy impaired results, was related to pre-operative myocardial structural abnormalities.

Adult↗
PubMed1997

O-GLYCBASE version 2.0: a revised database of O-glycosylated proteins.

O-GLYCBASE is an updated database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the literature, and from the SWISS-PROT database. Entries include information about species, sequence, glycosylation sites and glycan type. O-GLYCBASE is now fully cross-referenced to the SWISS-PROT, PIR, PROSITE, PDB, EMBL, HSSP, LISTA and MIM databases. Compared with version 1.0 the number of entries have increased by 34%. Revision of the O-glycan assignment was performed on 20% of the entries. Sequence logos displaying the acceptor specificity patterns for the GalNAc, mannose and GlcNAc transferases are shown. The O-GLYCBASE database is available through WWW or by anonymous FTP.

Algorithms↗
PubMed1997

Gene therapy of T helper cells in HIV infection: mathematical model of the criteria for clinical effect.

This paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction cells that is initially transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests that a 100% protection against viral escape must be obtained. The study also suggests that a gene therapy against HIV infection should be designed to give the transduced cells a partial but not necessarily total protection against HIV-induced cell death, and to avoid the production of viral mutants insensitive to the gene therapy.

Cell Death↗
PubMed1997

Impact of size mismatch and left ventricular function on performance of the St. Jude disc valve after aortic valve replacement.

BACKGROUND: The hemodynamic function of the St. Jude valve may change relative to changes in left ventricular function after aortic valve replacement for aortic stenosis. From theoretical reasons one may hypothesize that prosthetic valve hemodynamic function is related to left ventricular failure and mismatch between valve size and patient/ventricular chamber size. METHODS: Forty patients aged 24 to 82 years who survived aortic valve replacement for aortic stenosis with a standard St. Jude disc valve (mean size, 23.5 mm; range, 19 to 29 mm) were followed up prospectively with Doppler echocardiography and radionuclide left ventriculography preoperatively and 9 days, 3 months, and 18 months after the operation with assessment of intravascular hemolysis at 18 months. Follow-up to a maximum of 7.4 years (mean, 6.3 years) was 100% complete. RESULTS: Left ventricular muscle mass index decreased from 198 +/- 62 g.m-2 preoperatively to 153 +/- 53 g.m-2 at 18 months (p < 0.001), paralleled by a significant increase in left ventricular ejection fraction, peak ejection rate, and peak filling rate; only 18% of the patients had normal left ventricular muscle mass index and only 32% normal ventricular function (normal left ventricular ejection fraction, peak ejection rate, peak filling rate, early filling fraction, and late filling fraction during atrial contraction) at 18 months. Prosthetic valve peak Doppler gradient dropped from 20 +/- 6 mm Hg at 9 days to 17 +/- 5 mm Hg at 18 months (p < 0.05). Reduction of left ventricular muscle mass index was unrelated to peak gradient and size of the valve. Peak gradient at 18 months rose with valve orifice diameter of 17 mm or less (by 6 mm Hg), orifice diameter/body surface area of 9 mm.m-2 or less (by 5 mm Hg), left ventricular enddiastolic dimension (by 23 mm Hg per 10 mm increase), and impaired ventricular function (by 3 mm Hg). All but 2 patients (5%) had intravascular hemolysis; none had anemia. Two patients with moderate paravalvular leak had the highest serum lactic dehydrogenase levels; 4 patients with trivial leak had higher serum lactic dehydrogenase levels than those without leak. Serum lactic dehydrogenase levels rose with moderate paravalvular leak, impaired ventricular function, and valve orifice diameter. Six patients with trivial or moderate paravalvular leak had a cumulative 7-year freedom from bleeding and thromboembolism of 44% +/- 22% compared with 87% +/- 5% for those without leak (p < 0.05). CONCLUSIONS: The peak gradient of the St. Jude aortic valve dropped marginally over the first 18 postoperative months in association with incomplete left ventricular hypertrophy regression and marginal improvement of ventricular function. Mismatch between valve size and ventricular cavity size or patient size and impaired function of a dilated ventricle significantly compromised the performance of the St. Jude valve. Probably explained by platelet destruction or activation, paravalvular leak was related to bleeding and thromboembolic complications.

Adult↗
PubMed1997

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.

Chromosomes, Human, Pair 21↗
PubMed1997

Left ventricular systolic and diastolic function in aortic stenosis. Prognostic value after valve replacement and underlying mechanisms.

AIMS: The aims of the study were to examine the prognostic value of pre-operative left ventricular systolic and diastolic function on early, and late mortality after valve replacement for aortic stenosis, and to identify possible underlying mechanisms. METHODS AND RESULTS: Ninety-one prospectively recruited consecutive patients with a mean age of 61 years underwent valve replacement for aortic stenosis with concomitant coronary artery bypass grafting in 32 and a minimum postoperative observation period of 5.4 years. There were six early (< or = 30 days postoperatively) and 19 late deaths, and 18 deaths from specific causes (cardiac and prosthetic valve related). Early mortality occurred exclusively among patients with a combined subnormal left ventricular systolic function (subnormal ejection fraction or peak ejection rate, or supranormal time-to-peak ejection--duration of systole ratio) and a subnormal fast filling fraction. In Cox regression models on crude mortality and specific deaths, a subnormal ejection fraction and a fast filling fraction of < or = 45% were the only independent risk factors. Patients with none of these risk factors had normal sex- and age-specific survival, those with any one factor had an early, and those with both factors a massive early and a late excess mortality, with 5-year crude survival of 92%, 77%, and 50%, respectively (P < 0.0001). Systolic wall stress was without prognostic value. Further analyses indicated that impairment of left ventricular function occurred with increasing muscle mass over two phases: (1) diastolic dysfunction characterized by a pattern of severe relative concentric hypertrophy; (2) the addition of systolic dysfunction characterized by a more dilated, less concentric chamber geometry. Coronary artery disease seemed to provoke the latter development sooner. CONCLUSIONS: Impaired systolic and diastolic left ventricular function, irrespective of afterload, were decisive independent pre-operative risk factors for early as well as late mortality after aortic valve replacement for aortic stenosis. The adverse influence of concentric hypertrophy was the main underlying mechanism. Operative intervention, before impairment of diastolic and systolic function, should be advocated.

Adult↗
PubMed1997

Protein distance constraints predicted by neural networks and probability density functions.

We predict interatomic Calpha distances by two independent data driven methods. The first method uses statistically derived probability distributions of the pairwise distance between two amino acids, whilst the latter method consists of a neural network prediction approach equipped with windows taking the context of the two residues into account. These two methods are used to predict whether distances in independent test sets were above or below given thresholds. We investigate which distance thresholds produce the most information-rich constraints and, in turn, the optimal performance of the two methods. The predictions are based on a data set derived using a new threshold which defines when sequence similarity implies structural similarity. We show that distances in proteins are predicted more accurately by neural networks than by probability density functions. We show that the accuracy of the predictions can be further increased by using sequence profiles. A threading method based on the predicted distances is presented. A homepage with software, predictions and data related to this paper is available at http://www.cbs.dtu.dk/services/CPHmodels/.

Amino Acids↗
PubMed1997

Complement-mediated enhancement of HIV-1 infection in peripheral blood mononuclear cells.

We investigated if complement-mediated enhancement of HIV infection occurs in peripheral blood mononuclear cells (PBMC). In 7 experiments, we evaluated the effect of human complement on HIVIIIB infection in vitro. We measured HIV antigen production on day 4 and found that pre-incubation of HIV with complement led to enhanced production of antigen with a median enhancement of 2.5-fold (range 1.1-6.8). This complement-mediated increase in antigen production was statistically significant (p < 0.02). Complement-mediated enhancement of HIV infection was also tested in CD4 cells enriched from PBMC, and CD4 cells persistently gave higher levels of infection enhancement than PBMC. Thus, CD4 cells appear to be sufficient for complement-mediated enhancement of HIV infection to occur. In addition, we tested if it was possible to detect complement-mediated enhancement of primary HIV isolates in PBMC. We tested 3 isolates and found only a minor effect on antigen production (median enhancement 1.2-fold, range 0.6-1.5). Furthermore, addition of HIV-specific antibodies in combination with complement resulted in enhanced antigen production in 2/3 sera tested. However, the combination of complement and antibodies resulted in only a minor increase in enhancement of HIV infection compared to that obtained with complement alone. Finally, we found evidence of complement-mediated enhancement of HIV infection in resting PBMC. In conclusion, we demonstrated that complement-mediated enhancement of HIV infection does occur in vitro in PBMC.

CD4-Positive T-Lymphocytes↗
PubMed1997

M-mode echocardiography in aortic stenosis. Clinical correlates and prognostic significance after valve replacement.

To relate preoperative findings at M-mode echocardiography to preoperative clinical and haemodynamic status and to identify possible echocardiographic risk factors for mortality after aortic valve replacement (AVR), 250 patients with AVR for aortic stenosis (AS) were studied. In follow-up averaging 3.2 years there were 22 early (< 30 days) and 23 late deaths. Rising NYHA function class and cardiothoracic index, and left ventricular (LV) failure were related to rising LV end-diastolic and end-systolic diameter index (EDDI, ESDI), and to increasing LV muscle mass index and decreasing fractional shortening (FS). High peak-to-peak systolic aortic valve gradient and LV end-systolic pressure were related to small dimensions of LV with increased FS and posterior wall thickness (PWTh). EDDI < or = 20 mm/m2 and increasing PWTh were independent risk factors for early mortality. Patients with EDDI < or = 20 mm/m2 had normal or supranormal FS. PWTh was the only independent risk factor in long-term survival: 5-year rates being 81 +/- 6%, 94 +/- 3% and 85 +/- 7% for PWTh < or = 13, 14-17 and > or = 18 mm, respectively (p = 0.03). Prevalence of concomitant coronary artery disease (CAD) rose with decreasing PWTh. Angina pectoris in non-CAD patients was related to very high PWTh. Subnormal EDDI was associated with poor surgical outcome, and dilated, poorly contracting LV with congestive heart failure prior to AVR. The degree of LV hypertrophy seemed to be the dominant risk factor, but confounders included myocardial ischaemia due to CAD in low-grade hypertrophy or to hypertrophy per se. A hypothetically confounding factor is the reversibility potential of moderate or severe LV hypertrophy following AVR.

Aged↗
PubMed1996

O-GLYCBASE: a revised database of O-glycosylated proteins.

O-GLYCBASE is a comprehensive database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the SWISS-PROT and PIR databases as well as directly from recently published reports. Nineteen percent of the entries extracted from the databases needed revision with respect to O-linked glycosylation. Entries include information about species, sequence, glycosylation site and glycan type, and are fully referenced. Sequence logos displaying the acceptor specificity for the GaINAc transferase are shown. A neural network method for prediction of mucin type O-glycosylation sites in mammalian glycoproteins exclusively from the primary sequence is made available by E-mail or WWW. The O-GLYCBASE database is also available electronically through our WWW server or by anonymous FTP.

Amino Acid Sequence↗
PubMed1996

Prediction of the secondary structure of HIV-1 gp120.

The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV strain BH10 gp120, as well as in 27 other HIV-1 strains examined. Two helical segments were predicted in regions displaying profound sequence variation, one in a region suggested to be critical for CD4 binding. The predicted content of helix, beta-strand, and coil was consistent with estimates from Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design of future HIV subunit vaccine candidates.

Algorithms↗
PubMed1996

Relationship between protein structure and geometrical constraints.

We evaluate to what extent the structure of proteins can be deduced from incomplete knowledge of disulfide bridges, surface assignments, secondary structure assignments, and additional distance constraints. A cost function taking such constraints into account was used to obtain protein structures using a simple minimization algorithm. For small proteins, the approximate structure could be obtained using one additional distance constraint for each amino acid in the protein. We also studied the effect of using predicted secondary structure and surface assignments. The constraints used in this approach typically may be obtained from low-resolution experimental data. When using a cost function based on distances, half of the resulting structures will be mirrored, because the resulting structure and its mirror image will have the same cost. The secondary structure assignments were therefore divided into chirality constraints and distance constraints. Here we report that the problem of mirrored structures, in some cases, can be solved by using a chirality term in the cost function.

Protein Structure, Secondary↗
PubMed1996

Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic stenosis.

In a prospective study 99 consecutive patients with operative indication due to severe aortic stenosis (AS) were put on a surgical waiting list. The waiting-time to aortic valve replacement (AVR) averaged 6.3 months (0.5-19 months). There were 58 men and 41 women with a mean age of 61 years (21-82 years). The patients were divided into three groups: group I (n = 81) with an uneventful stay on the waiting list (including one patient who declined the AVR offer); group II (n = 11) with significant worsening of a prognostic index; and group III (n = 7) with patients who died during the waiting-time. The waiting-list death rate was 13.5 +/- 5.0% patient-year-1 compared with a post-AVR death rate of 4.9 +/- 0.9%. patient-year-1 (p < 0.05) with a mean post-AVR follow-up of 5.7 years. According to their prognostic index at inclusion, group II patients had a predicted (by a Cox model) 7-year post-AVR survival probability of 72%, but only of 61% according to their prognostic index immediately preoperatively; their observed 7-year post-AVR survival was 60%. Logistic regression analysis identified high age, short duration of symptoms, severe hypertrophy and strain in the ECG, female sex, and deranged left-ventricular diastolic function (related to severely increased left-ventricular muscle mass) as independent predictors of death on the waiting-list and prognosis worsening. From a clinical viewpoint, the predictive models did not allow sufficiently accurate identification of the patients at risk during the waiting-time. The consequences of a surgical waiting-time averaging 6 months are serious for AS patients. The death rate is high and a subgroup worsen their prognostic profile, with significantly reduced post-AVR long-term survival as the result.

Aortic Valve↗
PubMed1996

Distance distributions in proteins: a six-parameter representation.

We present a statistical analysis of protein structures based on interatomic C alpha distances. The overall distance distributions reflect in detail the contents of sequence-specific substructures maintained by local interactions (such as alpha-helixes) and longer range interactions (such as disulfide bridges and beta-sheets). We also show that a volume scaling of the distances makes distance distributions for protein chains of different length superimposable. Distance distributions were also calculated specifically for amino acids separated by a given number of residues. Specific features in these distributions are visible for sequence separations of up to 20 amino acid residues. A simple representation, which preserves most of the information in the distance distributions, was obtained using six parameters only. The parameters give rise to canonical distance intervals and when predicting coarse-grained distance constraints by methods such as data-driven artificial neural networks, these should preferably be selected from these intervals. We discuss the use of the six parameters for determining or reconstructing 3-D protein structures.

Amino Acid Sequence↗
PubMed1996

The potential for normal long term survival and morbidity rates after valve replacement for aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The sequelae of early aortic valve replacement (AVR) for aortic stenosis (AS) are controversial, with an increasing body of opinion regarding the patient risk profile as having an influence on long term survival and prosthesis-related morbidity rates. We therefore undertook a comparison of the morbidity and mortality rates of the patients undergoing AVR at our institution over a 22 year period with those in the background population to establish whether early intervention leads to an increased incidence of either. METHODS: A multivariate risk analysis of 630 consecutive patients with AS who were alive 30 days after AVR performed between January 1965 and December 1986 was completed. The patients had a mean age of 59 years (range 14-78 years), 98% received a mechanical prosthetic valve, and 71% were in functional classes III or IV preoperatively. RESULTS: Relative to an age- and sex-matched background population, the patients suffered a slight excess mortality during the first postoperative year, and a significant excess mortality after the 12th year, which was primarily related to congestive heart failure (64% of deaths versus 25% during the first 12 years; p < 0.01). A multivariate Cox regression model allowed calculation of a prognostic index for each patient. The index divided the patients into three groups (from low to high index): group A (n = 195) had normal sex- and age-specific survival, group B (n = 165) had a slight late (> 12th year) excess mortality, while group C (n = 270) had significant excess mortality throughout the follow up. Multivariate risk analysis of thromboembolism (1.7%/pt-yr), anticoagulant related hemorrhage (1.5%/pt-yr), all prosthesis-related complications combined (4.2%/pt-yr), and sudden cardiac events (arrhythmia and myocardial infarct; 1.8%/pt-yr) identified variables underlying advanced preoperative heart disease, coronary artery disease and systemic hypertension as the decisive risk factors. The preoperative prevalence of these risk factors as well as the postoperative incidence of the complications differed significantly between the three patient groups; A < B < C. Incidence rates of stroke in the patients (95% confidence interval) and in sex- and age-matched background populations were: group A, 0.48 (0.13-0.83) and 0.34 %/pt-yr, respectively, group B, 1.07 (0.46-1.68) and 0.52%pt-yr, respectively, and group C, 2.28 (1.50-3.06) and 0.68%/pt-yr respectively. Similar results were obtained for incidence rates of myocardial infarct. CONCLUSION: Operative intervention early in the course of AS, being equivalent to a favorable risk profile, may result in an age- and sex-specific normal long term survival, generally low rates of prosthesis-related complications and a normal incidence of the dominant thromboembolic and hemorrhagic events and of myocardial infarction.

Adolescent↗
PubMed1995

Prediction of O-glycosylation of mammalian proteins: specificity patterns of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase.

The specificity of the enzyme(s) catalysing the covalent link between the hydroxyl side chains of serine or threonine and the sugar moiety N-acetylgalactosamine (GalNAc) is unknown. Pattern recognition by artificial neural networks and weight matrix algorithms was performed to determine the exact position of in vivo O-linked GalNAc-glycosylated serine and threonine residues from the primary sequence exclusively. The acceptor sequence context for O-glycosylation of serine was found to differ from that of threonine and the two types were therefore treated separately. The context of the sites showed a high abundance of proline, serine and threonine extending far beyond the previously reported region covering positions -4 through +4 relative to the glycosylated residue. The O-glycosylation sites were found to cluster and to have a high abundance in the N-terminal part of the protein. The sites were also found to have an increased preference for three different classes of beta-turns. No simple consensus-like rule could be deduced for the complex glycosylation sequence acceptor patterns. The neural networks were trained on the hitherto largest data material consisting of 48 carefully examined mammalian glycoproteins comprising 264 O-glycosylation sites. For detection neural network algorithms were much more reliable than weight matrices. The networks correctly found 60-95% of the O-glycosylated serine/threonine residues and 88-97% of the non-glycosylated residues in two independent test sets of known glycoproteins. A computer server using E-mail for prediction of O-glycosylation sites has been implemented and made publicly available. The Internet address is NetOglyc@cbs.dtu.dk.

Algorithms↗